Known nebulizer vials for aerosol therapy are of plastic construction and use the venturi principle, in particular the so-called double venturi, in the sense that the air originating from a compressor is passed at high velocity through a small-diameter tube constricted internally (to form the venturi) and terminating with an orifice which emerges from the free surface of a solution of an aerosol therapy medicament contained in a reservoir. A nozzle is mounted concentrically on the end of said tube such that between the nozzle and the tube, there is an interspace communicating lowerly with the solution contained in the reservoir. The compressed air leaving the orifice of said tube causes the particles or droplets of the medicament solution to be sucked upwards through said interspace, to form an upwardly directed stream of solution particles, which leaves the nozzle orifice. The stream of solution particles formed in this manner is atomized (to form the aerosol) by causing the stream to strike against a flow breaker device positioned above the nozzle orifice. The flow breaker device is positioned at, but without completely closing, the lower end of a conduit through which external air can enter the vial following inhalation by the patient on an aerosol exit conduit with which the vial is provided.
As known to the expert of this sector, the characteristic parameters of a therapeutic aerosol are the mass median aerodynamic diameter (indicated by the initials MMAD which depends on the orifice diameter of the nozzle), the geometric standard deviation (indicated by the initials GSD) and the nebulization rate.
The MMAD provides an indication of the average dimensions of the particles forming the aerosol, this identifying the region of the air passageways in which the nebulized medicament will deposit.
The GSD enables the degree of dispersion of the solution particle dimensions within the distribution to be evaluated.
Finally, the nebulization rate is essentially an index of the mass of medicament nebulized per unit of time.
The MMAD and the GSD can both be obtained from the aerosol particle diameter distribution: the MMAD is in fact the aerodynamic diameter to which 50% of the aerosol particle diameter distribution corresponds; the GSD can be calculated from the particle diameter distribution graph, if the distribution is sufficiently linear between 10% and 90%, i.e. if the distribution is Gaussian, by using suitable extrapolation calculation methods (see ISO 9276-2).
The medical literature has established that, for therapeutic purposes, those regions of a patient""s respiratory tract reachable by the aerosol are related to the dimensions of the medical solution particles inhaled. More precisely, aerodynamic particle diameters greater than 5 microns are adequate for treatment of the upper air passages; diameters between 2 and 6 microns for the tracheobronchial region; diameters between 0.5 and 3 microns for alveolar administration. Reference should be made to the following texts for further details:
International Commission on Radiological Protection (1994): Human respiratory Tract Model for Radiological Protection. Annals of the ICRP Vol. 24, No. 1-3 Elservier Science Inc. Tarrytown N.Y.
Heyder J., Gebhart J., Rudolf G., Schiller C. F. and Stahlhofen W. (1986): Deposition of particles in the human respiratory tract in the size range 0.005-15 xcexcm Journal of Aerosol Science 17(5):811-825.
Stahlhofen W., Rudolf G., and James A. C. (1989): Intercomparison of Experimental Regional Deposition Data. Journal of Aerosol Medicine 2(3): 285-308.
From the aforegoing it is evident that to treat respiratory affections it is important that the dose of suitable medicament is administered only into the therapeutically appropriate region of the respiratory tract, to prevent wastage of medicament in addition to undesired systemic effects. To achieve this, a nebulizer vial must be used which is able to generate an aerosol of the precise particle size distribution characteristics.
An object of the present invention is therefore to provide a nebulizer vial for aerosol therapy which enables the MMAD to be varied.
It is also important that a nebulizer vial has a nebulization rate suitable for the type of patient to be treated. In this respect, although it is true that increasing the nebulization rate accelerates the therapy, a high nebulization rate, although suitable for normal adult patients, can be excessive for determined patients such as children or seriously asthmatic patients, to the extent of making correct administration of the medicament difficult.
Another object of the invention is therefore to provide a nebulizer vial of the aforestated type in which the nebulization rate can be varied.
As a nebulizer vial for aerosol therapy is often used for domiciliary treatment by non-expert persons and can be used repeatedly for different respiratory pathologies, a further object of the invention is to provide a vial of the aforesaid type in which the aerosol characteristics (particle size distribution and nebulization rate) can be varied on the basis of the patient""s therapeutic needs in a very simple manner within the ability of any patient.
The aforestated first object is attained by the nebulizer vial of the present invention, characterised in that, for diameter parity of the nozzle orifice, means are provided to vary the distance between the nozzle orifice and the flow breaker device. The flow breaker device may comprise a flow breaker diaphragm. In this respect, it has been verified that varying this distance varies the MMAD of the solution particles.
The means for varying said distance can comprise (for a predefined orifice diameter of the nozzle) nozzles of different length, to mount on the end of the compressed air tube (the flow breaker diaphragm being fixed), so also varying in consequence the distance between the orifice of the compressed air tube (which is always in the same position) and the orifice of the nozzle. Obviously, various series of nozzles can be provided which differ in the orifice diameter of the nozzles.
As an alternative the same nozzle can again be used, but with a means which, with one and the same nozzle fixed to the compressed air tube, enables either the elevation of the compressed air tube orifice to be varied (and consequently the elevation of the nozzle orifice), or the position of said flow breaker diaphragm to be varied relative to the compressed air tube orifice maintained in a fixed position.
Preferably on that surface of the flow breaker diaphragm facing the nozzle orifice there is provided coaxial with the nozzle orifice a peg which, on replacing the nozzle with another of different length or by vertically moving the flow breaker diaphragm (if the nozzle is not replaceable), approaches the nozzle orifice to a greater or lesser extent.
The aforestated second object is attained by providing a device for adjusting the flow of external air entering the vial as a result of inhalation by the patient, this enabling the nebulization rate of the nebulizer vial to be adjusted.
To attain the aforesaid final object the nebulizer vial is formed in two parts, of which a lower part contains the solution of medicament for aerosol therapy and comprises the compressed air feed tube and the relative nozzle, whereas the upper part comprises the flow breaker diaphragm, the inlet enabling external air to enter the vial following inhalation by the patient, and the aerosol exit conduit, the two parts being removably connected together.
The fact of forming the nebulizer vial in two parts as just described can be used to vary the distance between the nozzle orifice and the flow breaker diaphragm, the two said parts of the vial then being formed and connected together in such a manner as to be able to obtain different distances between the nozzle orifice and the flow breaker device.